Genetic regulation, physiology, assessment and inhibition of efflux pumps responsible for multi-drug resistant phenotypes of bacterial pathogens

The response of bacteria to a given antibiotic or other toxic agent that does not immediately kill them results in an adaptive response that secures their survival. This response may involve a number of distinct mechanisms, among which is the activation of genes that promote the appearance of transporters that extrude the agent prior to its reaching its target. These transporters extrude a large variety of chemically unrelated compounds and hence they bestow on the bacterium a multi-drug resistant (MDR) phenotype. The appearance of this MDR phenotype during therapy makes therapy problematic. Understanding the genetic and physiological properties of MDR efflux pumps is an absolute requirement if MDR bacterial infections are to be successfully managed. There is much to learn and methods that afford the needed understanding will eventually pave the way for the successful management of an MDR bacterial infection. Therefore, the application of recently developed methods that assess the MDR bacterium at its genetic and physiological levels is the focus of this chapter. The material presented in this chapter is only the beginning for the evaluation and assessment of MDR efflux pumps.